The local treatment of tissue by exposure to radiation-emitting material is now well established. Such treatment targets the tissue adjacent to the source while keeping the radiation effects on neighboring healthy tissue to a minimum. A major advantage of this form of treatment is that it concentrates the emitted radiation at the site where the treatment is needed, e.g. within a tumor, while keeping the amount of radiation transmitted to the healthy tissue far below what it otherwise would be if the radiation were beamed into the body from an external source, using teletherapy.
Radiation therapy implemented by placing a radiation source near or within the tissue to be treated, i.e., brachytherapy, is normally practiced in one of three ways: 1) by placing the source(s) within the tissue to be treated, i.e. interstitial therapy, 2) by placing the source(s) inside a body cavity, normally in association with a positioning device called an applicator, to irradiate tissue surrounding the cavity, i.e., intracavitary therapy, or 3) by placing the source(s) within a vessel or duct, normally in association with a catheter, to treat tissue surrounding the vessel or duct, i.e. intralumenal therapy.
A short segment of gold wire, generally called a “gold grain,” containing radiation-emitting gold isotopes such as gold-198, has been found to be a suitable implantable radioactive material. The advantage of using gold grains for interstitial implantation is that gold is compatible with the body. That is, gold neither degrades, dissolves, nor causes any toxic reaction within the body. Radon-222 encapsulated in platinum or other biocompatible metals has also been used in an implantable therapeutic device.
However, materials such as gold-198 and radon-222 have significant counter-indicating characteristics for interstitial tumor treatment in that they emit relatively penetrating radiation, such as high energy gamma radiation. Such high energy radiation not only subjects the patient's healthy tissue to more radiation than is desired, but in addition exposes medical personnel as well as other persons coming into contact with the patient, to significant doses of potentially harmful radiation. Therefore, it is often preferred to use radiation sources which emit lower energy radiation, such as those that emit low energy X-rays, or beta particles.
The use of capsules enclosing the radioactive material is necessary to contain the radioactive material, preventing it from becoming systemically distributed within the patient or escaping into the environment where it could contaminate medical personnel, medical facilities or the general environment. With the exception of gold grains cited above, such encapsulated radioactive material is referred to as “sources” or “seeds.”
The construction of the capsule should preferably allow the rapid and facile insertion of the seed into the organ or body part being treated, with minimal trauma to the surrounding tissue. Due to the small size of the capsules, which frequently have outer diameters of the order of 0.5 mm to 0.8 mm, and lengths of the order of 5 mm, a popular technique for implanting the seeds is to insert them into the body percutaneously using a hollow needle which is preloaded with the desired number of seeds and when the needle is in the desired location in the tissue, a stylet is used to hold the seeds in place while the needle is withdrawn from around them, leaving the seeds in the desired location. The use of such small radiation sources is a common way of practicing interstitial brachytherapy.
U.S. Pat. No. 3,351,049 describes seeds with an encapsulating outer shell containing the radiation-emitting isotope, iodine-125. Iodine-125 has a radiation spectrum that is favorable for interstitial use. The encapsulating shell localizes the radioactive iodine to the tumor treatment site by physically preventing the iodine-125 from migrating to other parts of the body. In particular, this technique protects the thyroid, a site of specific iodine uptake. Therefore, encapsulating an isotope permits the use of isotopes that would otherwise dissolve in the body and/or present potential toxic consequences to the patient. Physicians have employed capsules containing radiation-emitting iodine-125 as part of the treatment of patients with tumors.
U.S. Pat. Nos. 4,702,228 and 5,405,309 describe encapsulated seeds containing palladium-103 as the radioactive isotope. Palladium-103 is a radiation source possessing both a preferred radiation spectrum for therapeutic use and a preferred half-life. Palladium metal is insoluble in body fluids and has been injected as a powder directly into living tissue with no reported deleterious effects. Physicians also have used capsules containing palladium-103 for treating patients with tumors. The entire disclosure of each reference cited hereinabove and below is incorporated by reference.
Brachytherapy has met with increasing success over the past decade, in part due to the availability of more appropriate isotopes such as iodine-125 and palladium-103, and in part due to the recognition of the importance of placement of the seeds within the treatment volume and maintenance of that positioning throughout the therapeutic life of the seeds. The importance of positioning has led to such techniques as computer aided treatment planning routines based on ultrasound or computed tomographic images (Feygelman, V. et al, “A Spreadsheet Technique for Dosimetry of Transperineal Prostate Implants”, Medical Physics, 22, 97–100, 1995), ultrasound guided transperineal implantation for prostate cancer (Brosman, S. A. and Tokita, K., “Transrectal Ultrasound-Guided Interstitial Radiation Therapy for Localized Prostate Cancer”, Urology, 38, 372–376, 1991) and conformal brachytherapy for carcinoma of the prostate (Osian, A. D. and Nori, D., “Conformal Brachytherapy for Carcinoma of the Prostate”, Endocurietherapy/Hyperthermia Oncology, 10, 15–24, 1994).
Imaging technology is available which is capable of accurately locating the desired position for a seed, but holding the seed in the desired position has proven more difficult. U.S. Pat. Nos. 5,342,283, 5,030,195, 4,815,449, 4,754,745 and 4,697,575 all disclose devices intended to assist in initial placement and/or in maintaining placement of the seeds. The objective of all of the disclosed inventions is to provide a means to position discrete encapsulated sources. Positioning is of sufficient significance that a product based on U.S. Pat. No. 4,815,449 is commercially available. The expansion of brachytherapy to the treatment of additional disease types will be facilitated by, and in some cases will depend on, further improving positioning techniques.
The most common brachytherapy sources used for permanent interstitial implantation are small capsules, containing either iodine-125 or palladium-103, which are approximately 4.5 mm long and 0.8 mm in diameter. In some applications, such as prostate cancer therapy, the availability of a longer seed would be of value in maintaining positioning. However, due to the motion of the soft tissue surrounding the seed, vis-à-vis the rigid capsule of the seed, to use a longer seed would pose too great a likelihood of puncturing a surrounding organ or vessel.
A technique that improves the dose distribution without requiring a longer linear seed is the rigid seed string which is based on U.S. Pat. No. 4,815,449. This device consists of a linear array of iodine-125 seeds spaced at 1 cm center to center inside an absorbable suture material which has been stiffened by a proprietary process. One major drawback to using this device is that it has a tendency to become lodged in the implanting needle due to the effects of moisture on the suture material. Furthermore, this device does not include the ideal source, i.e., a continuous linear source, but rather relies on a series of separated, discrete sources in a line.
Clinical studies indicate brachytherapy sources could provide beneficial therapy in some tumor types where implantation of the seeds directly into the tissue is not possible, for example in the treatment of lung cancer (Nouri, D., “Intraoperative Brachytherapy in Non-Small Cell Lung Cancer”, Seminars in Surgical Oncology, 9, 99–107, 1993) In such cases it is useful to insert a series of seeds inside suture material so that they can be sewn into or over the diseased tissue. A commercial product is available from Amersham Healthcare, Model 6720 I-125 Seeds in Carrier, consisting of iodine-125 seeds, spaced at 1 cm center to center, inside suture material. While this product offers a means of attachment, it suffers from representing a series of separated discrete sources rather than a more desirable continuous line source.
Furthermore, a major drawback for metal-encapsulated seeds is that the encapsulating metal absorbs a significant fraction of the radiation emitted by the contained radioisotope, for example about 14% of the iodine-125 X-rays and 40% of the palladium-103 X-rays are absorbed in the encapsulating metal in the current commercial seeds. As a consequence, to obtain the desired radiation dose rate on the exterior of the seed, additional expensive isotope activity must be added to overcome the losses in the encapsulating metal. Also because it is necessary to seal the ends of the capsules, the effective thickness of the metal is not the same in all directions resulting in a radiation field around the seed which is not uniform, a fact that complicates treatment planning and raises the possibility of the existence of areas within the treatment volume in which the radiation dose is below that required to kill all tumor cells present.
Thus the current practice of brachytherapy based on the use of discrete encapsulated sources is limited by: 1) the need to associate groups of discrete seeds together by some means so that they can be placed into tissue in a predetermined array and held in that array throughout the therapeutic life of the sources, 2) the need for complex treatment planning that takes into account the discrete nature of the seeds and the shape of the radiation field around each seed with the assumption the field shape around each seed is the same, 3) the need to add excess expensive isotope to compensate for the radiation absorption in the encapsulating metal, and 4) the creation of a nonuniform radiation field around the source because the effective thickness of the encapsulating metal is not the same in all directions. The present invention as disclosed herein, significantly reduces each of these limitations and furthermore allows a more complete realization of the potential benefits of brachytherapy.
Definitions
The description of the present invention is facilitated by the use of the following terms which are used in this patent specification and the claims as defined herein:
The term “polymeric” means composed of organic polymers, including silicones, whether naturally occurring or synthetic, and whether homopolymers or copolymers.
A “radioactive composite” is a substance that consists essentially of a radioactive powder and a polymeric matrix. In accordance with the present invention, the particles of radioactive powder are dispersed within the polymeric matrix essentially randomly throughout a particular volume thereof.
“Therapeutic sources” that can be fabricated from the radioactive composite include a structure that is solid in cross section, e.g. a right circular cylindrical rod; a structure that is hollow in cross section, e.g. a right circular cylindrical hollow tube; a suture (such as a monofilament or a multifilament thread, cord or string); a mesh; a film; a sheet; and microscopic, essentially monodisperse spheroidal sources.
An “applicator” is a device used to conform a therapeutic source to the shape of a body cavity so as to hold it in place during the period of treatment. Examples of applicators include the Fletcher-Suit and Manchester applicators.
The “average dimension” of one of the very fine radioactive particles of the radioactive powder is the average of the maximum and the minimum dimensions of the generally irregularly shaped particles.